We have isolated an alpha-globulin serum suppressor factor, which is associated with immunoglobulin G, and have shown that it is immunochemically related to the sheep erythrocyte (E) receptors of human peripheral blood T lymphocytes. This suppressor factor has been named soluble E receptor (SER). Subsequent radioimmunoassay showed that the level of SER is elevated in the sera and ascites of patients with cancer, viral infections and liver cirrhosis. It bears no direct correlation to serum IgG levels but bears significant correlation to its ability to depress the DNA synthesis induced by phytohemagglutinin (r = 0.45) in human peripheral blood lymphocytes. Sandwich radioimmunoassays developed on the detergent solubilized cellular E receptor indicate that the cellular E receptor (CER) can also be detected in the sera of patients with cancer and some autoimmune diseases. We shall attempt to delineate the chemical relationship of these two suppressor factors and to establish their clinical applications.